Diabetes mellitus is classified into type 1 diabetes mellitus and type 2 diabetes mellitus. About 95% of the patients suffer from type 2 diabetes mellitus. For treating diabetes mellitus and/or complications thereof, there have been used various agents, for example, agents for stimulating insulin secretion (such as sulfonylurea derivatives, meglitinide derivatives, etc.), agents for improving insulin resistance (such as biguanide derivatives, thiazolidinedione derivatives, etc.), agents for inhibiting carbohydrate digestion (such as alpha-glucosidase inhibitors, etc.), incretins (such as GLP-1 analogs, DPP-4 inhibitors, etc.) (Current Opinion in Drug Discovery & Development, 2009, 12). However, it is well-known in the art that the agents for stimulating insulin secretion, which are most commonly used, cause side effects such as hypoglycemia, weight gain, etc. In addition, it have been reported that the biguanide derivatives show side effects such as lactic acidosis, etc.; and that the thiazolidinedione derivatives show side effects such as hepatic toxicity, heart failure, etc. (D. D. Sears et al., Proc Natl Acad Sci USA 2009; 106: 18745-18750).
Meanwhile, G protein-coupled receptor also known as GPR119 is mainly expressed in pancreatic islets and in the gastrointestinal tract. GPR119 activation mediates insulin secretion through direct action on pancreatic β-cells; and stimulates the glucagon-like peptide-1 (GLP-1) secretion in the intestinal L-cells, thereby improving glucose stimulated insulin secretion (GSIS) (Lina M. L. et al., Diabetes 2009; 58: 1058-1066). Therefore, it is expected that an agent for activating GPR119 increases glucose homeostasis, thereby being able to be used as a potential agent for treating diabetes mellitus as well as inhibiting food intake and weight gain. In fact, there are various reports that GPR119 agonists show fat loss and weight loss through various obesity animal models (Matias I. et al., Br J Pharmacol 2007; 152(2): 676-690, Hansen H. S. et al., Biochemical Pharmacology 78 (2009) 553-560, Hiroyuki O. et al., Life sciences 92 (2013) 167-173).
The stimulation of insulin secretion by GPR119 activation can avoid potential hypoglycemia, since it makes glucose-dependent insulin secretion possible through stimulating the formation of cyclic adenosine monophosphate (cAMP) in the β-cells. The GLP-1 secretion and cAMP activation by continuous GPR119 activation increase the islet beta cell mass, which improves self-insulin production, thereby making it possible to treat insulin-dependent diabetes mellitus (Ansarullah et al., Plos one 2013; 8(1):1-11, Gao J. et al., Transplant International 2011 European Society for Organ Transplantation 24 (2011) 1124-1134). Therefore, it is expected that GPR119 agonists may be continuously used as an agent for treating diabetes mellitus for long duration, while minimizing the side effects (e.g., hypoglycemia, weight gain) of conventional hypoglycemic agents or anti-diabetic agents.